Year: 2018
Type: conference-abstract
Abstract: Pediatric high-grade gliomas (pHGG) account for the most cancer-related deaths in children under the age of 19 years old. Recent advances have demonstrated that pHGGs drastically differ from their adult counterparts in terms of genetic and epigenetic alterations, suggesting they may also differ in the constituency of their tumor microenvironment. It is now known tumor associated macrophages (TAMs) can make up 30–40% of the total tumor cell mass in adult high-grade gliomas and play important roles in immune suppression and tumor promotion. This raises the question of whether pHGGs possess a distinct constituency of TAMs due to their unique genetic and epigenetic landscapes. To uncover the composition and behavior of TAMs in pHGG we utilize RCAS/tva, a somatic cell-type specific gene transfer system in which we administer RCAS-PDGFA or RCAS-PDGFB to simulate PDGF receptor activation in immune-competent new-born mice. We found that PDGFB-driven tumors have a significantly lower median survival compared to PDGFA-driven tumors. PDGFB-driven tumors also have increased infiltration of TAMs, made evident by immunohistochemical staining for IBA1. Flow cytometry analysis indicates the increased number of TAMs is due to an increased inflammatory monocyte population, but not due to the microglial population. We hypothesize these findings are attributable to the additional activation of the stromal population by PDGFB, as it can activate both PDGFRα and PDGFRβ while PDGFA only activates PDGFRα. Gene expression analysis indicates that several chemokines, chemokine receptors, macrophage, and immune markers are differentially expressed between PDGFB and -A tumor types. To establish correlations between PDGF signaling and TAM infiltration in human pediatric tumor samples, we stained 37 tumors for IBA1, PDGF-receptors, and PDGF-ligands. A positive correlation exists between high PDGFRb and PDGFB staining with high IBA1. Further studies will be done to discern the effects of increased TAM infiltration and the mechanisms driving enhanced tumor malignancy.
Source: Neuro-Oncology
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2900136703